With the rapidly growing elderly U.S. population, a better understanding of how alcohol and nutrition interact to protect against or accelerate cognitive decline and age-related brain changes could have profound implications for public health. A large proportion of the adult population regularly consumes alcohol but little is known about how mid and later life alcohol use impacts cognitive function and brain integrity in old age. Even less is known about whether nutrition, which may interact with alcohol at behavioral and physiological levels, influences cognitive function and brain structure. This interdisciplinary proposal, involving experts in epidemiology, cognitive neuroscience, neuroimaging and biostatistics will analyze existing as well as newly collected data from a large, population-based NIH-funded cohort study of older adults, now in its 39th year, the RBS (The Rancho Bernardo Study, RBS; Dr. Barrett-Connor, P.I.). The RBS has an exceptionally rich database for exploring the association of mid and late life alcohol consumption with cognitive function. It contains measures of alcohol intake, including data on frequency, amount and type of alcohol consumed obtained up to 7 times on a given participant over ~25 year period, cognitive function tests assessing different cognitive domains obtained up to 6 times on a given participant over ~20 year follow-up period, and detailed dietary information from up to three administrations of the Harvard Willett Food Frequency questionnaire over ~10 years. It also contains a large number of medical health-related variables, validated medication use, mood and lifestyle measures, which will allow control for numerous potentially confounding covariates and effect modifiers. Analysis of this existing data will allow us to determine how current and prior alcohol use relates to change in cognitive function over time in older adults and how nutrition influences these associations, while controlling for relevant covariates such as education level, smoking, physical activity, medical status (e.g. diabetes, cardiovascular disease), cardiovascular disease risk factors, and medications. We will also collect a comprehensive set of sensitive structural MRI and diffusion tensor imaging (DTI) data, using state-of-the-art image acquisition and analysis procedures, from a subset (n=300) of RBS participants who showed a range of alcohol use at baseline. This will allow us to examine how past and current alcohol use relates to measures of late-life brain structural integrity, and assess whether nutrition modifies these associations, whie controlling for numerous covariates. This study will increase basic knowledge of the association of alcohol and diet on cognitive function and brain health in the elderly, and could result in lifestyle recommendations to promote successful cognitive and brain aging. Because age-related cognitive impairment is a major contributor to loss of independence and lower quality of life in older adults, and because care for cognitively impaired individuals places an enormous financial burden on society, improved understanding of whether and how modifiable behaviors affect cognitive function in aging could have enormous public health impact.